Approach to headache

Fadila Naji, MD
Department of Family Medicine
AUB-MC
Introduction
-Among the most common medical complaints

-No epidemiology or long introduction today

-When a patient presents with headache, the
clinician must answer the following questions:
(1) Is the headache "worrisome"?
(2) If the headache is benign, what type is it?
(3) How is the acute headache best treated?
(4) How may future headaches be prevented?

Step 1- R/O WORRISOME CAUSES
Danger signs

1.Sudden onset of headache, or severe
persistent headache that reaches maximal
intensity within a few seconds or minutes
after the onset of pain, is very suggestive
of
- Malignancy
- SAH

Ex: SAH often presents with the abrupt onset of excruciating pain
/ migraine generally begins with moderate pain and then gradually
increases to a maximal level over 1 to 2 hours
Question
One of the benign causes of headache may
cause a sudden onset of very severe
headache
reaching its maximal intensity in minutes to
hours.. You have to keep it in mind while
investigating more serious causes

Guess what type it is??
Cluster headache may sometimes be
confused with a serious headache, since
the pain from a cluster headache can reach
full intensity within minutes

However, cluster headache is transient
(usually lasting less than one to two hours)
and is associated with characteristic
ipsilateral autonomic signs such as tearing
or rhinorrhea
Danger signs

2.The absence of similar headaches in
the past:

The "first" or "worst" headache of my
life is a description that sometimes
accompanies an . or ..
- SAH
- CNS infection
Danger signs
3.A worsening pattern of headache
suggests a
or .. or .
-mass lesion
-subdural hematoma
-medication overuse headache

4.Focal neurologic symptoms other than
typical visual or sensory aura should raise
suspicion for .. or .
-mass lesion
-AV malformation
Danger signs..
5. Fever associated with headache may
be caused by intracranialor systemic
infections
Remember that an infection in a non-intracranial
location (such as the lungs or paranasal or mastoid
sinuses) may serve as a nidus for the development
of meningitis or intracranial abscess
Danger signs..
6. Any change in mental status, personality, or
fluctuation in the level of consciousness
suggests .. Or .. Or ..
-CNS inf
-growing tumor
-expanding subdural hematoma

7. The rapid onset of headache with exercise,
raises the possibility of . Or ..
-carotid artery dissection
-Raised intracranial pressure
More danger signs..
8. Head pain that spreads into the lower
neck and between the shoulders may
indicate:
meningeal irritation due to either
infection or subarachnoid blood
9. New headache in patients under the
age of 5 or over the age of 50
10. New headache type in a patient with
cancer suggests metastasis
More danger signs
11. New onset headache during
pregnancy or postpartum suggests
possible:
-cortical vein or venous sinus
thrombosis
-carotid dissection
-pituitary apoplexy
-pre-eclampsia
If according to this quick evaluation, a
serious cause of headache has been
ruled out, go to the step 2:
Evaluate the type of the benign
headache
The 3 most common causes of
benign headache:
1- Tension Headache
2- migraine headache
3-cluster headache
Which type is more prevalent,
migraine or tension headache??

Tension-type headache seems to be
more prevalent than migraine

Both migraine and tension-type
headaches affect more often than
. , while cluster headache is
predominantly a disorder of ..

Symptom Migraine
headache
Tension headache Cluster headache
Location

Unilateral in 60 to
70% ; bifrontal or
global in 30%
Bilateral

Always unilateral,
usually begins around
the eye or temple
Characteristics Gradual in onset,
crescendo pattern;
pulsating; moderate or
severe intensity;
aggravated by routine
physical activity
Pressure or tightness
which waxes and
wanes

Pain begins quickly,
reaches a crescendo
within minutes; pain is
deep, continuous,
excruciating, and
explosive in quality
Patient appearance Patient prefers to
rest in a dark, quiet
room
Patient may remain
active or may need to
rest

Patient remains active
Duration 4 to 72 hours Variable

30 minutes to 3 hours
Associated symptoms Nausea, vomiting,
photophobia,
phonophobia; may
have aura (usually
visual, but can involve
other senses or cause
speech or motor
deficits)
none Ipsilateral lacrimation
and redness of the
eye; stuffy nose;
rhinorrhea; pallor;
sweating; focal
neurologic symptoms
rare; sensitivity to
alcohol
Dont miss sinusitis but don t over
diagnose it!
Dont forget to keep in mind sinusitis as a
potential cause of headache

Sinusitis is being wrongly over diagnosed
as a cause of headachesometimes with
absence of its essential clinical features..

Dont forget that migraine could be
associated with nasal congestion, runny
nose, facial heaviness upon bending
forward
Always keep in mind

Overalp of headache causes

Sinusitis ------------- Migraine
General evaluation: history
Age at onset
Presence or absence of aura and prodrome
Frequency, intensity and duration of
attack
Time and mode of onset
Quality, site, and radiation of pain
Associated symptoms and abnormalities
Family history of migraine
Precipitating and relieving factors
Effect of activity on pain
Response to any previous treatment
Cont history
Association with recent trauma
Any recent changes in sleep, weight, or
diet
State of general health
Change in work or lifestyle
Change in method of birth control
(women)
Effects of menstrual cycle
Specific features suggesting
specific causes

Chronic nasal stuffiness or chronic
respiratory infection suggests a
diagnosis of ..
Sinusitis

Specific features suggesting specific
causes
Visual field defects suggest the presence of

Lesion of the optic pathway (eg, due to a
pituitary mass)

Blurring of vision on forward bending of the
head, headaches upon waking early in the
morning that improve with sitting up, and
double vision or loss of coordination and balance
should raise the suspicion of ; this
disorder should also be considered in patients
with chronic, daily, progressively worsening
headaches associated with chronic nausea
Raised intracranial pressure

Specific features suggesting specific
causes
Sudden, severe, unilateral vision loss
suggests the presence of
optic neuritis

Headache, fatigue, generalized aches and
pain, and night sweats in subjects age 55
years or older suggest the presence of ..
temporal arteritis

Intermittent headaches with high blood
pressure are suggestive of
pheochromocytoma
Physical examination
The majority of patients with headache
have a completely normal physical and
neurologic examination:

Obtain blood pressure and pulse

Palpate the head, neck, and shoulder
regions

Check temporal and carotid arteries

Complete neuro exam

Warning signs on PE
Neck stiffness

Papilledema

Focal neurologic signs
Indications for imaging studies

Any alarm sign urgent brain imaging

Remaining patients, no RCTs that help
delineate when imaging is necessary

The decision to scan or not to scan in
headache is likely to remain one of
clinical judgment
The American Academy of Neurology,
American Academy of Family Physicians,
American College of Physicians-
American Society of Internal Medicine,
and four other groups formed a
consortium and issued a year 2000
practice guideline that came to the
following conclusions regarding the need
for brain imaging in patients with
headache:


Neuroimaging should be considered in
patients with non acute headache and an
unexplained abnormal finding on neuro
exam

Neuroimaging is usually not warranted for
patients with migraine and a normal neuro exam,
although a lower threshold for imaging is
warranted in patients with atypical migraine
features or in patients who do not fulfill the
strict definition of migraine

Data insufficient to make a specific
recommendation for patients with tension-type
headache

Data insufficient to make a specific
recommendation regarding the relative
sensitivity of MRI compared with CT in patients
who have an imaging study performed
Given the lack of definitive data, one
approach is to consider neuroimaging in the
following situations:
-Recent significant change in the pattern,
frequency or severity of headaches
-Progressive worsening of headache
despite appropriate therapy
-Focal neurologic signs or symptoms
-Onset of headache with exertion, cough,
or sexual activity
-New onset of headache after age 40
years
The data are insufficient to recommend CT
or MRI when neuroimaging is deemed
necessary

A head CT scan (without and with
contrast) is likely to be sufficient in most
patients

An MRI along with MRA are indicated
when posterior fossa or vascular lesions
are suspected
Quick review of one of the
most common benign
headache causes:
MIGRAINE
Migraine
Migraine is an episodic headache that may be
classified into three types:
Migraine with aura (old term: classic migraine)
Migraine without aura (old term: common
migraine)
Migraine variants (retinal migraine,
ophthalmoplegic migraine, familial hemiplegic
migraine)

Pathophysiology
Polygenetic and multifactorial etiology

The popular vascular theory of migraine
(headache caused by vasodilatation, while aura
results from vasoconstriction) is no longer
considered viable in its original form
Pathophysiology: Current state of knowledge
The
primary
event :
?
Brainstem
generator
The 1ary event: ? Brainstem
generator
Study that used PET scan found increased blood
flow in the brainstem during migraine attacks

Injection of sumatriptan induced complete relief
from headache, but the brainstem activation
persisted

Pathophysiology: current state of knowledge
Which part of brainstem?


locus ceruleus??
Pathophysiology: current state of knowledge
Locus ceruleus
Locus
ceruleus
2ndary event: from brainstem to
cortex

Locus ceruleus projections to the
cerebral cortex may initiate cortical
hypoperfusion and cortical spreading
depression of Laeo , which can explain
the aura and the following pain of
migraine
Pathophysiology: current state of knowledge
What is cortical spreading
depression of Leao?

A self propagating wave of neuronal and
glial depolarization that spreads across
the cerebral cortex


Pathophysiology: current state of knowledge
Cortical spreading depression of
Leao

Cause the aura of migraine

Activation of the trigeminovascular
nociceptive pathways


Pathophysiology: current state of knowledge
Trigeminovascular system
Cortical spreading depression

Activation of the trigeminal nucleus caudalis,
nucleus tractus solitarius and dorsal raphe nucleus

Release of substance P, calcitonin gene-related
peptide, and other vasoactive polypeptides
Dilatation of blood vessels
innervated by trigeminal nerve
Pathophysiology: current state of knowledge
Role of serotonin

Low serotonin state results in a deficit in the
serotonin descending pain inhibitory system,
facilitating activation of the
trigeminovascular nociceptive pathways in
conjunction with cortical spreading depression

Pathophysiology: current state of knowledge
Role of CGRP
37 amino acid neuropeptide expressed in
trigeminal ganglia nerves/ potent vasodilator
of cerebral and dural vessels

Stimulation of the trigeminal ganglion
induces the release of CGRP, and CGRP
infusion can trigger a migraine attack in
migraineurs

Elevated CGRP levels are normalized
following administration of triptans,
suggesting that these may act to control
migraine at least in part by reducing CGRP
levels

Epidemiology
Prevalence is high: up to 17 % of women and 6
percent of men

Most common in those aged 30 to 39

Three times more common in women than men

Migraine with/without?? aura is the most
common type, accounting for approximately
80 % of cases
Migraine and obesity
Mounting evidence suggests that
obesity is associated with an
increased frequency and severity of
migraine
Migraine Triggers
Food and beverages (containing nitrites,
glutamate, aspartame, tyramine)
Disturbed sleep pattern
Hormonal changes
Drugs &compounds (nitroglycerin, histamine,
reserpine, estrogens, corticosteroid withdrawal,
hydralazine, perfumes, smoke..)
Physical exertion
Sensory stimuli (visual, auditory, olfactory..)
Weather changes
Hunger
Psychological factors
Phases of Acute Migraine

Premonitory symptoms
Aura
Headache
1.Premonitory symptoms

Precede a migraine attack by several
hours to one or two days

Typical symptoms include fatigue,
concentration difficulty, neck rigidity,
sensitivity to light or sound, nausea,
blurred vision, pallor


2.Typical Migraine aura
Complex of neurologic symptoms that
presents as a progressive neurologic
deficit or disturbance with complete
recovery

Thought to be caused by CSD occurring in
regions of the cortex corresponding to
the clinical manifestations of the aura

Typically occurs before the onset of
migraine headache, and the headache
usually begins simultaneously with or just
after the end of the aura phase

Migraine aura: typical manifestations
Visual disturbances +++
start with a flickering uncolored zig-zag line in the
center of the visual field and gradually progress
toward the periphery of one hemifield, often leaving a
scotoma

Sensory symptoms (Numbness and tingling of the lips,
lower face, and fingers of one hand) (cheilo-oral)

Motor weakness (typical motor aura involves the hand
and arm on one side)

Speech disturbances

Atypical Migraine aura
Headache onset can rarely occur an hour
or more after the end of the aura phase

Aura can develop during or after the onset
of headache

Some patients have migraine aura with
only a minimal or no subsequent headache

Most auras resolve in less than one hour,
although motor auras may persist longer
(indicative of complicated migraine in the
IHS classification scheme)

Rare aura
Rarely, auras persist for longer
than one week or are associated
with infarcts on brain imaging;
these are indicative of
migrainous infarction
3.Headache

Commonly begins early in the morning but can
occur at any time

Headache is lateralized during severe migraine
attacks in 60 to 70% of patients

The pain is usually gradual in onset, following a
crescendo pattern with gradual but complete
resolution

Pain is usually dull, deep, and steady when mild
to moderate; it becomes throbbing or pulsatile
when severe
IHS diagnostic criteria of
migraine without aura
Headache attacks last 4 to 72 hours
Headache has at least two of the following
characteristics: unilateral location;
pulsating quality; moderate or severe
intensity; aggravation by routine physical
activity
During headache at least one of the
following occurs: nausea and/or vomiting;
photophobia and phonophobia
At least five attacks occur fulfilling the
above criteria
History, PE, and neuro exam do not suggest
any underlying organic disease

IHS diagnostic criteria of
migraine with aura
A headache that has the features of migraine
without aura, with:
At least 2 attacks of aura with migraine
headache

The migraine aura fulfills criteria for one of
the subforms of aura with migraine headache

The symptoms are not attributed to another
disorder

IHS criteria for typical migraine
aura

Visual and/or sensory and/or speech symptoms

Gradual development

Duration no longer than .
1h
A mix of positive and negative features

Complete reversibility
Abortive treatment/
Prophylactic treatment
Abortive treatment

-Simple analgesics

-Migraine specific agents
Acute treatment of migraine:
abortive therapy

More effective if given early in the
course of the headache

Which strategy does work better, a large
single dose or repetitive small doses ????
Large single dose



Many oral agents are ineffective in
migraineurs, because of ..
poor absorption secondary to migraine-
induced gastric stasis

Medication-induced headache
A common disorder related to medication
overuse (analgesic rebound headache)

Almost any acute headache medication can
be implicated

In order to prevent MIH, acute medications
should be limited to no more than , and
preventive therapies should be used as the
mainstay in patients with frequent headaches
10 days per month
MILD ANALGESICS (NSAIDS)
NSAIDs with reported efficacy in randomized,
placebo-controlled trials of migraine therapy :
ibuprofen (400 to 1200 mg)
naproxen (750 to 1250 mg)
diclofenac (50 to 100 mg)
diclofenac epolamine (65 mg)
tolfenamic acid (200 mg)
aspirin(650 to 1000 mg)
indomethacin suppo (50 mg)

No studies comparing the relative efficacy of
different NSAIDs
Triptans
Specific" therapy for acute migraine
Inhibits the release of vasoactive
peptides
Blocks pain pathways in the brainstem
Inhibits transmission in the trigeminal
nucleus caudalis, thereby blocking
afferent input to second order neurons;
this effect is probably mediated by
reducing the levels of CGRP
Triptans
Available triptans: sumatriptan,
zolmitriptan, naratriptan, rizatriptan,
almotriptan, eletriptan, and frovatriptan
In lebanon: Sumatriptan & Rizatriptan
Number of RCT and systematic reviews
found all of the triptans effective for the
treatment of acute migraine
Few trials have compared the triptans
head to head, making it difficult to decide
whether to use one versus another
In Lebanon..
IMIGRAN - 50mg- 100mg 30,000 LL-
66,863 LL B NSSF . Box 2 :
Sumatriptan (succinate)

MAXALT - 10mg 39,134 LL B NSSF. Box
2-3
Rizatriptan (benzoate) 10mg


Triptans

Best response to treatment when
initiated while headache intensity is
mild and within . of onset
1h



Triptans: Limitations to use
Familial hemiplegic migraine
Basilar migraine
Ischemic stroke
Ischemic heart disease
Uncontrolled hypertension
Pregnancy
It may be prudent to give the first dose
of the drug under medical supervision for
patients with risk factors but no known
CAD(men over the age of 40 and
postmenopausal women, and patients with
controlled vascular risk factors such as
DM, DL, and HTN)


Triptans:Limitations to use

Should not be used within 24 hours of
the use of ergotamine preparations
(double CVD risk)

Triptans:Limitations to use
FDA issued a public health advisory in July
2006 to warn about the possible risk of
serotonin syndrome associated with
concomitant use of triptans and SSRIs or
SNRIs

Risk appears to be very small

Combination can be used in most cases
where both are needed as long as the risks
and benefits are discussed, and patients
are monitored for symptoms of serotonin
syndrome
Ergotamine

It is unclear if it is the ergotamine itself or
the other ingredients in the combination drugs
that provide the most effect

There are two observations that question the
efficacy of ergotamine alone:
Oral and rectal ergotamine have a very poor
bioavailability (2 and 5 %, respectively)
Controlled trials of oral ergotamine alone have
failed to show efficacy in the relief of
migraine
Ergotamine
May worsen the nausea and vomiting
associated with migraine

Vascular occlusion and rebound headaches have
been reported with oral doses exceeding 6
tablets per 24 hours or 10 tablets per week

Years of use also may be associated with
valvular heart disease
Ergotamine
Should be avoided in patients with CAD
because they cause sustained coronary
artery constriction, PVD, HTN

Overuse has been associated with an
increased risk of cerebrovascular,
cardiovascular, and peripheral ischemic
complications, particularly among those
using cardiovascular drugs

Should not be used in patients who have
migraine with prolonged aura because they
may reduce cerebral blood flow
Dihydroergotamine (DHE 45)
Often used in combination with an
antiemetic drug, and this is always the case
when it is given by IV administration

Metoclopramide is known to be effective
for migraine when used alone

In several studies DHE combined with
metoclopramide was superior to other
agents combined with the same antiemetic,
suggesting that DHE 45 does have
independent efficacy for migraine

In Lebanon..

Dihydroergotamine mesylate. SEGLOR -
5mg 18,183 LL B NSSF. Box 30

CAFERGOT 7,860 LL B NSSF. Box 20
Caffein/ Ergotamine tartrate

Prophylactic therapy
Indications of prophylactic therapy
Prophylactic headache treatment is
indicated if the headaches are
Frequent (more than .. headaches per mo)
4
Long lasting (longer than .. hours)
12
Account for a significant amount of total
disability
Contraindication to or failure or overuse of
acute therapies

Goals of prophylactic therapy
The AAN practice parameters notes that
the goals of preventive therapy are to

Reduce attack frequency, severity and
duration

Improve responsiveness to treatment of
acute attacks

Improve function and reduce disability

Prophylactic therapy for
uncommon migraine
Based on expert consensus, prophylactic
therapy also should be considered to
prevent neurologic damage in the presence
of uncommon migraine conditions including

Hemiplegic migraine
Basilar type migraine
Migraine with prolonged aura
Migrainous infarction

What are the options for
prophylactic treatment???

Anti-hypertensive

Anti-epileptic

Anti-depressants
ANTIHYPERTENSIVES
Blood pressure treatment appears to reduce
the overall prevalence of headache

There is clinical trial data showing that beta
blockers, CCBs, ACE inhibitors, and ARBs are
effective for migraine prevention

Of these, the evidence for migraine
prevention is strongest for beta blockers
Beta blockers
Several RCTs studies have found that chronic
therapy with propranolol reduces the
frequency and severity of migraine in 60 to
80 percent of patients

Only propranolol and timolol have been
approved by the FDA

It can take several weeks for these drugs to
become effective, the dose should be
titrated and maintained for at least .
months before deeming the medication a
failure
3

Calcium channel blockers
Widely used for migraine prophylaxis

May relieve aura symptoms as well as prevent
migraines

Verapamil is frequently the FIRST CHOICE for
prophylactic therapy based upon ease of use
and a favorable side effect profile

Tolerance may develop with calcium channel
blockers; starting after eight weeks of
successful therapy
ACE inh/ ARB
A double-blind, placebo controlled,
crossover study of 60 patients with two to
six migraine episodes per month found that
lisinopril (10 mg/day for one week, then 20
mg/day) significantly reduced the number
of hours and days with headache and
headache severity compared with placebo

Similar results were reported with the
angiotensin II receptor blocker (ARB)
candesartan
Antidepressants

TCAs (eg, amitriptyline and clomipramine)
are effective in preventing chronic
migraines

Insufficient data to draw conclusions
about the SSRIs

It is not clear whether the effect of
antidepressants is independent of
depression

Anticonvulsants
Sodium valproate, gabapentin, and
topiramate are more effective than
placebo for reducing the frequency of
migraine attacks

Both valproate and topiramate are
approved by the US FDA for migraine
prophylaxis

Prophylactic principles


Start the drug at a low dose. Increase the dose
gradually until therapeutic benefit develops, the
maximum dose of the drug is reached, or side
effects become intolerable

Give the chosen medication an adequate trial in
terms of duration and dosage

Clinical trials suggest efficacy is often first noted
at four weeks and can continue to increase for three
months


Prophylactic principles

Slowly taper the drug if the headaches are
well controlled. Many patients experience
continued relief with either a lower dose or
cessation of the medication

The choice of prophylactic agent depends
upon associated medical problems, and
presence of comorbid conditions such as
depression, mania, anxiety, panic, Raynaud's
syndrome, epilepsy


Doses.
Inderal : start 20mg qid, increase 20-
40mg/dose every 3-4 weeks/max: 160-240mg/d

Isoptin: 80 bid, then 80 tid

Tryptizol: start 10-25 mg qd at btmax
150mg/d

Topiramate: Initial: 25 mg QD (in evening); may
increase weekly by 25 mg/day up to the
recommended dose of 100 mg/day given in 2
divided doses. Doses >100 mg/day have shown no
additional benefit

Cluster headache
The pathogenesis of cluster headache is
complex and remains incompletely understood

The most widely accepted theory is that
primary cluster headache is characterized by
hypothalamic activation with secondary
activation of the trigeminal-autonomic reflex,
probably via a trigeminal-hypothalamic pathway
Attacks of severe unilateral orbital,
supraorbital, or temporal pain, accompanied by
autonomic phenomena
Unilateral autonomic symptoms are ipsilateral
to the pain and may include ptosis, miosis,
lacrimation, conjunctival injection, rhinorrhea,
and nasal congestion
Attacks usually last 15 to 180 minutes. In the
episodic form, attacks occur daily, usually one
to eight times a day for some weeks, followed
by a period of remission. The chronic form of
cluster headache lacks sustained remissions.
Cluster headache, in its typical form, is
unmistakable. The diagnosis is
exclusively a clinical one
For patients with acute cluster headache, initial
treatment with either triptans or
oxygen (Grade 1A)

Oxygen should be tried first if available since
it is without side effects. Otherwise,
subcutaneous sumatriptan 6 mg can be used as
initial therapy for patients with no
contraindications

For patients with acute cluster headache who
do not respond to or tolerate oxygen and
triptans, alternatives include
intranasal lidocaine and oral ergotamine
Preventive therapy should be started as soon as
possible at the onset of a cluster episode, with
the goal of suppressing attacks over the
expected duration of the cluster period
For patients with chronic cluster headache and
those with relatively long-lasting (ie, two
months or longer) active periods of episodic
cluster headache, we recommend initial
preventive therapy with verapamil (Grade 1B).

The onset of benefit is dose dependent. The
starting dose is usually 240 mg daily in three
divided doses. Most patients respond to a total
dose of 240 to 320 mg daily. Titration to a
total dose of up to 960 mg daily may be
necessary for some patients to obtain full
prophylactic benefit.
For patients with episodic cluster headache
who have active cluster periods that last less
than two months, we suggest initial preventive
therapy with glucocorticoids alone (Grade 2C)

Prednisone 60 to 100 mg once a day for at least
five days, followed by a taper with a dose
reduction of 10 mg daily
MCQs
Which one of the following is an indication for
migraine prophylaxis treatment:
a. Duration of attacks exceeding 3 hours
b. Frequency of attacks exceeding 3 per month
c. Frequency of attacks exceeding 4 per month
d. All patients with migraine regardless to
response to abortive treatment

All the following are considered categories of
migraine prophylaxis treatment, except:
A. Category of anti-hypertensives
B. Category of anti-depressants
C. Category of opioids
D. Category of anti-epileptics